Although growth of microvessels has been studied in normal maturation, wound healing, tumor growth, exercise, and several systemic diseases, there exists no consensus on the factors requisite for blood vessel growth or remodelling. The long-term objective of this research is to establish the role of mechanical stresses in the regulation of microvascular network remodelling. To accomplish this, it is necessary to document the topological and dimensional changes in network structure that result from the application of known stress fields. The specific objective of this study is to test the hypothesis that intravascular stresses, namely blood pressure and wall shear stress, play a role in determining the sites and magnitudes of vessel growth. Better understanding of vessel remodelling mechanisms may lead to improved therapeutic strategies, such as stimulation of capillary growth in hypertensive heart, improvement of red cell distribution in hypertensive muscle, and limitation of tumor growth.
The specific aims of this work are to measure the remodelling of the microvasculature in the gracilis muscle of the rat during normal maturation of WKY rats and during development of spontaneous hypertension in SHR and to relate the observed remodelling to the hemodynamic stresses acting in the network. This will be achieved by incorporating measured data on network topology, vessel dimensions, and perfusion pressures into a quantitative model of the microvasculature in skeletal muscle. Arteriolar, venular, and capillary network reconstructions will be obtained by image-analysis of ink-filled muscle specimens and histological cross-sections. Reference diameter distributions will be measured using in-vivo epi-fluorescence microscopy, and blood pressures in the feeding and draining vessels of the muscle will be measured using the servo-null micropipette method. The hemodynamic network model will then allow determination of pressure, flow, and wall shear stress distribution in the network, making it possible to examine the relation of hemodynamic stresses to network structure in subsequent stages of development. By applying this method to both WKY and SHIR, a test can be made of the hypothesis that the elevated resistance in spontaneous hypertension is an adaptation to changes in hemodynamic conditions, but is based on a common growth principle.
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